Publications by authors named "Ruth Quintana"

4 Publications

  • Page 1 of 1

Novel Pathway of Adenosine Generation in the Lungs from NAD: Relevance to Allergic Airway Disease.

Molecules 2020 Oct 27;25(21). Epub 2020 Oct 27.

Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.

Adenosine and uric acid (UA) play a pivotal role in lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). In the present experiments, we measured adenosine synthesis from nicotinamide adenine dinucleotide (NAD) in membranes prepared from wild type (WT) and CD38 knockout (CD38KO) mouse lungs, from cultured airway smooth muscle and epithelial cells, and in bronchoalveolar lavage fluid after airway challenge with epidemiologically relevant allergens. Adenosine was determined using an enzymatically coupled assay that produces ATP and is detected by luminescence. Uric acid was determined by ELISA. Exposure of cultured airway epithelial cells to extract caused significant nucleotide (NAD and ATP) release in the culture media. The addition of NAD to membranes prepared from WT mice resulted in faster generation of adenosine compared to membranes from CD38KO mice. Formation of adenosine from NAD affected UA and ATP concentrations, its main downstream molecules. Furthermore, NAD and adenosine concentrations in the bronchoalveolar lavage fluid decreased significantly following airway challenge with house-dust mite extract in WT but not in CD38KO mice. Thus, NAD is a significant source of adenosine and UA in the airways in mouse models of allergic airway disease, and the capacity for their generation from NAD is augmented by CD38, a major NADase with high affinity for NAD. This novel non-canonical NAD-adenosine-UA pathway that is triggered by allergens has not been previously described in the airways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25214966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663290PMC
October 2020

Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity.

Neuron 2020 03 15;105(6):1036-1047.e5. Epub 2020 Jan 15.

Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Dopamine is involved in physiological processes like learning and memory, motor control and reward, and pathological conditions such as Parkinson's disease and addiction. In contrast to the extensive studies on neurons, astrocyte involvement in dopaminergic signaling remains largely unknown. Using transgenic mice, optogenetics, and pharmacogenetics, we studied the role of astrocytes on the dopaminergic system. We show that in freely behaving mice, astrocytes in the nucleus accumbens (NAc), a key reward center in the brain, respond with Ca elevations to synaptically released dopamine, a phenomenon enhanced by amphetamine. In brain slices, synaptically released dopamine increases astrocyte Ca, stimulates ATP/adenosine release, and depresses excitatory synaptic transmission through activation of presynaptic A receptors. Amphetamine depresses neurotransmission through stimulation of astrocytes and the consequent A receptor activation. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the dopamine- and amphetamine-induced synaptic regulation, revealing a novel cellular pathway in the brain reward system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2019.12.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322729PMC
March 2020

Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks.

Elife 2016 12 24;5. Epub 2016 Dec 24.

Department of Neuroscience, University of Minnesota, Minneapolis, United States.

Interneurons are critical for proper neural network function and can activate Ca signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABA receptors, potentiation involved astrocyte GABA receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABA receptor () knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.20362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231406PMC
December 2016

Strain-specific regulation of striatal phenotype in Drd2-eGFP BAC transgenic mice.

J Neurosci 2012 Jul;32(27):9124-32

Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

Mice carrying bacterial artificial chromosome (BAC) transgenes have become important tools for neuroscientists, providing a powerful means of dissecting complex neural circuits in the brain. Recently, it was reported that one popular line of these mice--mice possessing a BAC transgene with a D(2) dopamine receptor (Drd2) promoter construct coupled to an enhanced green fluorescent protein (eGFP) reporter--had abnormal striatal gene expression, physiology, and motor behavior. Unlike most of the work using BAC mice, this interesting study relied upon mice backcrossed on the outbred Swiss Webster (SW) strain that were homozygous for the Drd2-eGFP BAC transgene. The experiments reported here were conducted to determine whether mouse strain or zygosity was a factor in the reported abnormalities. As reported, SW mice were very sensitive to transgene expression. However, in more commonly used inbred strains of mice (C57BL/6, FVB/N) that were hemizygous for the transgene, the Drd2-eGFP BAC transgene did not alter striatal gene expression, physiology, or motor behavior. Thus, the use of inbred strains of mice that are hemizygous for the Drd2 BAC transgene provides a reliable tool for studying basal ganglia function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.0229-12.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461272PMC
July 2012